Alkylsalicylaldehydes have so far been synthesised according to the Reimer Tiermann reaction but this process has important drawbacks: low yield and use of chloroform. Document «New progress in aromatic aldehyde production technology» published in «Journal of Synthetic Organic Chemistry, 1991, 49(3): 195-204» describes this reaction in details.
Another route has been described in document U.S. Pat. No. 4,351,962 by reaction of alkylphenol with boronic acid as an intermediate followed by formaldehyde addition. The alcohol intermediate formed is further oxidised by molecular oxygen in the presence of a platinum or palladium catalyst. However, this process is complex and the required conditions are harsh.
Document U.S. Pat. No. 5,399,761 describes an improved synthesis by reacting a phenolic compound and formaldehyde. The synthesis reaction is called formylation of phenols. More specifically, this document describes the oximation of 2-hydroxyarylsalicylaldehyde. The 2-hydroxyarylsalicylaldehyde is synthesised by formylation of magnesium bis-nonylphenoxide. The solvent used is toluene or xylene.
The document “Magnesium-mediated ortho-Specific Formylation and Formaldoximation of phenols” (Aldred et al., J. Chem. Soc. Perkin Trans., 1, 1994, 1823-1831) describes in details the formylation reaction of phenol derivatives with magnesium methoxide to produce the corresponding salicylaldehyde derivatives, and the oximation of said salicylaldehyde derivatives to produce the corresponding salicylaldoxime derivatives. Methanol and toluene are the typical solvent used during the synthesis reaction.
Document WO 2007/034501 discloses a new process for the manufacture of 5-nonylsalycylaldoxime in a two steps reaction involving a novel catalyst mixture comprising magnesium methoxide. Typically, the solvent used in this reaction is toluene.
Despite great advance in the formylation process, there is still a need to improve the process related to the preparation of alkylsalicylaldehyde or its corresponding metallic salts, especially with respect to:                an improved yield; and        an improved productivity by reducing the synthesis reaction time.        